Methods of array data wave correction

Abstract

The invention relates to methods of correcting auto-correlated wave artifacts of array signal data based on the GC content of the nucleic acids under consideration without affecting signal variations due to copy number variations.

1 . A method for correcting wave artifacts of hybridization signal data, the method comprising the steps of:
 (a) segmenting observed hybridization signal data of a test and a control sample that hybridize to a set of probes, each probe covering a probe-binding section of the control sample;   (b) for each probe, determining at least one GC content value of at least one genomic region that comprises at least one probe-binding section;   (c) performing multi-variable polynomial regression analysis using the at least one GC content value determined in step (b) as an explanatory variable and the observed hybridization signal data as a response variable, to produce predicted hybridization signal data for each probe; and   (d) subtracting the predicted hybridization signal data from the observed hybridization signal data to obtain corrected hybridization signal data.   
     
     
         2 . The method of  claim 1 , wherein the genomic region is between about 50 and about 1,000,000 nucleotides in length. 
     
     
         3 . The method of  claim 1 , wherein the genomic region is about 572 nucleotides in length. 
     
     
         4 . The method of  claim 1 , wherein the genomic region is about 60 nucleotides in length. 
     
     
         5 . The method of  claim 1 , further comprising the step of empirically determining an optimal size of the genomic region. 
     
     
         6 . The method of  claim 1 , wherein the observed hybridization signal data is empirically determined. 
     
     
         7 . The method of  claim 1 , wherein the observed hybridization signal data of the test sample and the control sample comprises a log signal of the test sample and a log signal of the control sample. 
     
     
         8 . The method of  claim 1 , wherein the observed hybridization signal data of the test sample and the control sample comprises a log ratio of hybridization signal data of the test sample and the control sample. 
     
     
         9 . The method of  claim 1 , wherein the observed hybridization signal data is produced in a comparative genomic hybridization assay. 
     
     
         10 . The method of  claim 9 , wherein the data is segmented using a CGH segmentation algorithm. 
     
     
         11 . The method of  claim 1 , wherein the observed hybridization signal data is produced in a ChIP-chip assay. 
     
     
         12 . The method of  claim 1 , wherein the observed hybridization signal data is produced in a DNA methylation array assay. 
     
     
         13 . A method for identifying copy number variations in a test sample, the method comprising the steps of:
 (a) providing a set of probes that cover probe-binding segments of the test sample during hybridization;   (b) hybridizing to the probes a control sample labeled with a first label and a test sample labeled with a second label, such that observed hybridization signal data are produced;   (c) segmenting the observed hybridization signal data of the test and the control sample;   (d) for each probe, determining at least one GC content value of at least one genomic region that comprises at least one probe-binding section;   (e) performing multi-variable polynomal regression analysis using the GC content values determined in step (d) as an explanatory variable and the observed hybridization signal data as a response variable, to produce predicted hybridization signal data for each probe; and   (f) subtracting the predicted hybridization signal data from the observed hybridization signal data to obtain corrected hybridization signal data.   
     
     
         14 . The method of  claim 13 , wherein the genomic region is between about 50 and about 1,000,000 nucleotides in length. 
     
     
         15 . The method of  claim 13 , wherein the genomic region is about 572 nucleotides in length. 
     
     
         16 . The method of  claim 13 , wherein the genomic region is about 60 nucleotides in length. 
     
     
         17 . The method of  claim 13 , wherein steps (c)-(f) are performed using a log signal of the test sample and a log signal of the control sample as the observed hybridization signal data. 
     
     
         18 . The method of  claim 13 , wherein steps (c)-(f) are performed using a log ratio of the hybridization data of the test and the control sample as the observed hybridization signal data. 
     
     
         19 . The method of  claim 13 , wherein the segmentation is performed using a CGH segmentation algorithm.